Chapter 1 │ Page 21 2. RATIONALE, OBJECTIVES AND THESIS OUTLINE NTP represents, considering the established anti-cancer e ects, proven ICD-inducing potential and favorable safety profile, a highly localized and welltolerated therapeutic strategy with the potential to act as an e ective adjuvant to standard-of-care treatments. By enhancing treatment cytotoxicity and tumor immunogenicity, NTP could serve as an innovative approach to bridge conventional and immune-based therapies, ultimately improving treatment outcomes in cancer with high clinical need, like HNSCC. Therefore, I delineated my vision as follows: The main goal of this PhD dissertation was to investigate the immunestimulatory potential of NTP in the context of cancer therapy, with a particular focus on its future integration into combination strategies to enhance tumor immunogenicity and therapeutic e icacy. To achieve this, the following objectives were defined: 1. Emphasize the importance of proper experimental design of ROS-related studies, particularly in the context of immunology and cancer therapy research 2. Investigate the potential of NTP to enhance anti-tumor immunity in a novel NTPCDDP combination strategy for HNSCC 3. Evaluate the immunomodulatory capacities of NTP-induced oxidation on tumor-associated NK cell ligands and their role in shaping the tumor-immune landscape in a computational-experimental approach 4. Establish the importance of intercellular communications and discuss gap junction potential in cancer immunology and therapeutic strategies The chapters are designed to contribute to the central theme of this dissertation - immune stimulation via NTP to improve therapeutic outcomes - going from fundamental observations to mechanistic insights, and therapeutic applications to future opportunities and perspectives (Figure 2).
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